Project Summary (Project 5) The overall objective of the proposed study is to test the following hypotheses: longitudinal change in obesity during childhood, enhanced by low birth weight for gestational age, is (race- and sex-specifically) associated with adult cardiometabolic risk, and metabolomic profiles independently predict cardiometabolic risk and mediate the associations between longitudinal change in obesity during childhood and adult cardiometabolic risk. This objective will be achieved by 3 Specific Aims: 1) examine the (race- and sex-specific) associations of longitudinal change in obesity during childhood, independently and in combination with low birth weight for gestational age, with hypertension, type 2 diabetes, dyslipidemia, and non-alcoholic fatty liver disease in middle age; 2) examine the (race- and sex-specific) associations of longitudinal change in obesity during childhood, independently and in combination with low birth weight for gestational age, with subclinical measures of arterial and cardiac structure/function in middle age; and 3) identify novel metabolites profiled by state-of-the-art metabolomic technologies that predict progression of subclinical atherosclerosis, and test whether these metabolites mediate the associations between longitudinal changes in obesity during childhood and progression of subclinical atherosclerosis in middle age. These specific aims will be examined in 2,100 participants (420 participants for Specific Aim 3) whose cardiometabolic risk factors have been well characterized since early childhood, from the ongoing Bogalusa Heart Study. Findings from the proposed study will provide new insights into the early life origins of adult cardiometabolic risk, identify new metabolic pathways and offer new intervention/treatment strategies for cardiometabolic diseases in adults. Ongoing research projects in the Bogalusa Heart Study cohort, supported by peer-reviewed NIH grants, make the proposed project very cost-efficient. The COBRE will provide funding and protected time for the junior investigator to extend his research to metabolomics, a promising research front for cardiometabolic diseases and accumulate pilot data and publications for future R01 applications. In addition, the outstanding mentor team will greatly facilitate the junior investigator's smooth transition to research independence.